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Horm Metab Res 2011; 43(2): 117-120
DOI: 10.1055/s-0030-1267917
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Serum Levels of the Adipokine Fasting-induced Adipose Factor/Angiopoietin-like Protein 4 Depend on Renal Function

T. Baranowski1 , [*] , S. Kralisch1 , [*] , A. Bachmann1 , U. Lössner1 , J. Kratzsch2 , M. Blüher1 , M. Stumvoll1 , M. Fasshauer1
  • 1University of Leipzig, Department of Internal Medicine III, Leipzig, Germany
  • 2University of Leipzig, Institute of Laboratory Medicine, Leipzig, Germany
Further Information

Publication History

received 12.07.2010

accepted 27.09.2010

Publication Date:
22 October 2010 (online)

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Abstract

Fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/Angptl4) was recently introduced as a novel adipokine influencing glucose and lipid homeostasis. In the current study, we quantified circulating FIAF/Angtl4 levels in patients on chronic hemodialysis (CD) as compared to controls with a glomerular filtration rate above 50 ml/min. FIAF/Angptl4 was determined by ELISA in control (n=60) and CD (n=60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation, in both groups. Median serum FIAF/Angptl4 levels were more than 5-fold higher in CD patients (48.3 μg/l) as compared to control subjects (8.4 μg/l) (p<0.001). Furthermore, serum creatinine independently predicted FIAF/Angptl4 concentrations in multiple regression analyses in control subjects (p<0.01). In CD patients, C-reactive protein was independently and positively associated with circulating FIAF/Angptl4 (p<0.01). Taken together, we show that serum FIAF/Angptl4 levels are significantly increased in end-stage renal disease and independently associated with markers of renal function in control subjects.

Key words

FIAF/Angptl4 - hemodialysis - insulin resistance - obesity

References

  • 1 Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance.  Diabetologia. 2003;  46 1594-1603
    Google Scholar
  • 2 Trujillo ME, Scherer PE. Adipose tissue-derived factors: impact on health and disease.  Endocr Rev. 2006;  27 762-778
    Google Scholar
  • 3 Fasshauer M, Paschke R, Stumvoll M. Adiponectin, obesity, and cardiovascular disease.  Biochimie. 2004;  86 779-784
    Google Scholar
  • 4 Kralisch S, Sommer G, Deckert CM, Linke A, Bluher M, Stumvoll M, Fasshauer M. Adipokines in diabetes and cardiovascular diseases.  Minerva Endocrinol. 2007;  32 161-171
    Google Scholar
  • 5 Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B, Wahli W. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene.  J Biol Chem. 2000;  275 28488-28493
    Google Scholar
  • 6 Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spiegelman BM. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation.  Mol Cell Biol. 2000;  20 5343-5349
    Google Scholar
  • 7 Dutton S, Trayhurn P. Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes.  Br J Nutr. 2008;  100 18-26
    Google Scholar
  • 8 Yamada T, Ozaki N, Kato Y, Miura Y, Oiso Y. Insulin downregulates angiopoietin-like protein 4 mRNA in 3T3-L1 adipocytes.  Biochem Biophys Res Commun. 2006;  347 1138-1144
    Google Scholar
  • 9 Yoshida K, Shimizugawa T, Ono M, Furukawa H. Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase.  J Lipid Res. 2002;  43 1770-1772
    Google Scholar
  • 10 Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, Xu JY, Chen B, Chow WS, Tso AW, Lam KS. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice.  Proc Natl Acad Sci USA. 2005;  102 6086-6091
    Google Scholar
  • 11 Mandard S, Zandbergen F, van Straten E, Wahli W, Kuipers F, Muller M, Kersten S. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity.  J Biol Chem. 2006;  281 934-944
    Google Scholar
  • 12 Koliwad SK, Kuo T, Shipp LE, Gray NE, Backhed F, So AY, Farese Jr RV, Wang JC. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor) is a direct glucocorticoid receptor target and participates in glucocorticoid-regulated triglyceride metabolism.  J Biol Chem. 2009;  284 25593-25601
    Google Scholar
  • 13 Stejskal D, Karpisek M, Reutova H, Humenanska V, Petzel M, Kusnierova P, Vareka I, Varekova R, Stejskal P. Angiopoietin-like protein 4: development, analytical characterization, and clinical testing of a new ELISA.  Gen Physiol Biophys. 2008;  27 59-63
    Google Scholar
  • 14 Kersten S, Lichtenstein L, Steenbergen E, Mudde K, Hendriks HF, Hesselink MK, Schrauwen P, Muller M. Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids.  Arterioscler Thromb Vasc Biol. 2009;  29 969-974
    Google Scholar
  • 15 Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.  J Am Soc Nephrol. 2002;  13 134-141
    Google Scholar
  • 16 Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine RBP-4 in relation to renal function.  Diabetes Care. 2007;  30 2588-2592
    Google Scholar
  • 17 Sommer G, Ziegelmeier M, Bachmann A, Kralisch S, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of adipocyte fatty acid binding protein are increased in chronic haemodialysis.  Clin Endocrinol (Oxf). 2008;  69 901-905
    Google Scholar
  • 18 Pfau D, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine chemerin in relation to renal function.  Diabetes Care. 2010;  33 171-173
    Google Scholar
  • 19 Stein S, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine FGF21 depend on renal function.  Diabetes Care. 2009;  32 126-128
    Google Scholar
  • 20 Seeger J, Ziegelmeier M, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine vaspin in relation to metabolic and renal parameters.  J Clin Endocrinol Metab. 2008;  93 247-251
    Google Scholar
  • 21 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
    Google Scholar
  • 22 Cumin F, Baum HP, Levens N. Leptin is cleared from the circulation primarily by the kidney.  Int J Obes Relat Metab Disord. 1996;  20 1120-1126
    Google Scholar
  • 23 Sharma K, Considine RV, Michael B, Dunn SR, Weisberg LS, Kurnik BR, Kurnik PB, O’Connor J, Sinha M, Caro JF. Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.  Kidney Int. 1997;  51 1980-1985
    Google Scholar
  • 24 Campean V, Neureiter D, Varga I, Runk F, Reiman A, Garlichs C, Achenbach S, Nonnast-Daniel B, Amann K. Atherosclerosis and vascular calcification in chronic renal failure.  Kidney Blood Press Res. 2005;  28 280-289
    Google Scholar
  • 25 Folsom AR, Peacock JM, Demerath E, Boerwinkle E. Variation in ANGPTL4 and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study.  Metabolism. 2008;  57 1591-1596
    Google Scholar
  • 26 Adachi H, Fujiwara Y, Kondo T, Nishikawa T, Ogawa R, Matsumura T, Ishii N, Nagai R, Miyata K, Tabata M, Motoshima H, Furukawa N, Tsuruzoe K, Kawashima J, Takeya M, Yamashita S, Koh GY, Nagy A, Suda T, Oike Y, Araki E. Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis.  Biochem Biophys Res Commun. 2009;  379 806-811
    Google Scholar

1 These authors contributed equally to this work

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M. Fasshauer

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